@article{bibcite_4006,
  author = {Mohammed R. Shaker and Andrii Slonchak and Bahaa Al-mhanawi and Sean D. Morrison and Julian D. J. Sng and Justin Cooper-White and Alexander A. Khromykh and Ernst J. Wolvetang},
  title = {Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2},
  abstract = {Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2{\textendash}induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21{\textendash}encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2{\textendash}induced neuropathogenesis.},
  year = {2024},
  journal = {Science Advances},
  volume = {10},
  pages = {eadj4735},
  month = {2024-06-05},
  url = {https://www.science.org/doi/10.1126/sciadv.adj4735},
  doi = {10.1126/sciadv.adj4735},
}